Björkland A, Lööf L, Mendel-Hartvig I, Tötterman T H
Department of Clinical Immunology and Transfusion Medicine, University Hospital, Uppsala, Sweden.
J Immunol. 1994 Sep 15;153(6):2750-7.
Anti-mitochondrial Abs (AMA) of the M2 type are recognized as being specific for primary biliary cirrhosis (PBC). We developed a highly specific assay to detect single AMA-producing cells using pyruvate dehydrogenase (PDH), the major Ag for AMA. Total Ab and AMA production of in vivo activated B cells was measured in peripheral blood from 13 PBC patients, 22 patients with other liver diseases, and 15 healthy controls. Anti-PDH-producing cells, PDH spot-forming cells (PDH-SFC), were detected in 12 of 13 PBC patients and represented a very high proportion of circulating Ig-producing lymphocytes (9 +/- 8.6%; mean +/- SD). The autoantibodies were mainly of IgG and IgM Ig classes. The number of PDH-SFC was positively correlated with the numbers of total Ig-SFC within each Ig class. An increased number of total IgM SFC in blood was found in PBC patients compared with controls, and IgM SFC correlated with the elevated serum levels of IgM typical for this disease. Among the lymphocytes extracted from PBC liver tissue (n = 5), we detected PDH-SFC of IgG (range 0 to 33% of total SFC), IgM (0 to 42%), and IgA types (1 to 30%). IgA PDH-SFC were found in five of five livers, but only in two of thirteen blood samples investigated. Taken together, our data reveal that very high numbers of B cells spontaneously produce disease-specific autoantibodies in blood and liver tissue in PBC. Furthermore, the Ig class distribution of produced autoantibody differs between these two compartments, and this may have pathogenetic significance.
M2型抗线粒体抗体（AMA）被认为是原发性胆汁性肝硬化（PBC）的特异性抗体。我们开发了一种高度特异性的检测方法，利用丙酮酸脱氢酶（PDH）（AMA的主要抗原）来检测单个产生AMA的细胞。对13例PBC患者、22例其他肝病患者和15名健康对照者外周血中体内活化B细胞的总抗体和AMA产生情况进行了检测。在13例PBC患者中的12例中检测到产生抗PDH的细胞，即PDH斑点形成细胞（PDH-SFC），其在循环产生Ig的淋巴细胞中占很高比例（9±8.6%；平均值±标准差）。自身抗体主要为IgG和IgM免疫球蛋白类别。PDH-SFC的数量与每个免疫球蛋白类别中总Ig-SFC的数量呈正相关。与对照组相比，PBC患者血液中总IgM SFC数量增加，且IgM SFC与该疾病典型的血清IgM水平升高相关。在从PBC肝组织中提取的淋巴细胞（n = 5）中，我们检测到了IgG型（占总SFC的0至33%）、IgM型（0至42%）和IgA型（1至30%）的PDH-SFC。在5个肝脏中的5个均发现了IgA PDH-SFC，但在所检测的13份血液样本中仅在2份中发现。综上所述，我们的数据表明在PBC患者的血液和肝组织中有大量B细胞自发产生疾病特异性自身抗体。此外，所产生的自身抗体在这两个部位的免疫球蛋白类别分布有所不同，这可能具有致病意义。
